Growth hormone plus low-protein diet reduces BMD in rats

Abstract

Protein deficiency is known to decrease circulating GH and insulin-like growth factor I (IGF-I) levels in rats, as well as reducing bone mass and strength, and to impair IGF-I in humans, which is associated with an increased risk for fracture, explain Patrick Ammann and co-workers from the University Hospitals of Geneva in Switzerland.

Advertisement

To investigate whether GH treatment can correct bone metabolism in animals fed low-protein diets, the team fed female rats isocaloric diets with 2.5% or 15.0% casein for 2 weeks, followed by a 4-week schedule of bovine GH (0.5 or 2.5 mg/kg) or a vehicle control.

The animals’ proximal tibias were examined for BMD, bone strength, and histomorphometry.

As reported in the journal Bone, administration of GH led to a dose–dependent increase in levels of plasma IGF-I in animals fed a low-protein or normal diet.

However, animals given a low-protein diet also exhibited a GH dose–dependent loss in BMD and bone strength that was not seen in rats fed the normal diet who showed no BMD changes.

Levels of osteocalcin were significantly increased in rats given GH within 2 weeks of treatment - regardless of their diet - indicating greater bone formation. However, osteocalcin was lower in animals fed a low-protein compared with those fed a normal diet.

The ratio of deoxypyridinoline to creatinine was dose–dependently increased, indicating greater bone resorption in GH-treated animals, again regardless of diet, note the researchers, but this was only significant in low-protein rats.

“These results emphasize the major importance of dietary protein intake in the bone response to short-term GH to ensure a positive bone balance, and that caution will need to be employed when considering GH therapy in situations of compromised nutritional status,” conclude Ammann et al.

“These data also highlight the need for longer-term investigations into the therapeutic use of GH, and particularly regarding treatment options for the frail elderly.”